ABCB1 structural models, molecular docking, and synthesis of new oxadiazolothiazin-3-one inhibitors

Camillo Rosano, Maurizio Viale, Barbara Cosimelli, Elda Severi, Rosaria Gangemi, Alessia Ciogli, Daniela De Totero, Domenico Spinelli

Research output: Contribution to journalArticle

Abstract

Docking methods are powerful tools for in silico screening and drug lead generation and optimization. Here, we describe the synthesis of new inhibitors of ABCB1 whose design was based on construction and preliminary confirmation of a model for this membrane transporter of the ATP-binding cassette family. We chose the strategy to build our three-dimensional model of the ABCB1 transporter by homology. Atomic coordinates were then assayed for their reliability using the measured activity of some oxadiazolothiazin-3-one compounds. Once established their performance by docking analysis, we synthesized new compounds whose forecasted activity was tested by MTT and cytofluorimetric assays. Our docking model of MDR1, MONBD1, seems to reliably satisfy our need to design and forecast, on the basis of their LTCC blockers ability, the inhibitory activity of new molecules on the ABCB1 transporter.

Original languageEnglish
Pages (from-to)694-698
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume4
Issue number8
DOIs
Publication statusPublished - Aug 8 2013

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Keywords

  • ABCB1 inhibitors
  • docking
  • drug design
  • LTCC blockers compounds
  • multidrug resistance
  • oxadiazolothiazin-3-ones

ASJC Scopus subject areas

  • Organic Chemistry
  • Drug Discovery
  • Biochemistry

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